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Spatial determinates of effector and memory CD8+ T cell fates
Brigette C Duckworth1,2, Raymond Z Qin1,2, Joanna R Groom1,2
1Division of Immunology, Walter and Eliza Hall Institute of Medical Research, Parkville, Vic, Australia.
Immunological Reviews
|December 9, 2021
Summary
CD8+ T cell differentiation into short-lived effector cells (TSLEC) occurs in lymph node interfollicular regions, while stem-like memory cells (TSCM) differentiate in the paracortex. This spatial segregation is regulated by chemokine signals, influencing T cell fate.
Area of Science:
- Immunology
- Cell Biology
- Microscopy
Background:
- Lymph nodes are crucial for adaptive immunity, pathogen clearance, and cancer immunosurveillance.
- Intranodal migration of CD8+ T cells is essential for their activation and differentiation within the lymph node.
- Understanding T cell spatial regulation is key to controlling immune responses.
Purpose of the Study:
- To explore the spatial regulation of T cell fates within intact lymph nodes.
- To identify the inflammatory and chemokine regulators of spatially restricted T cell differentiation, focusing on promoting stem-like memory cells (TSCM).
- To investigate the orchestration of intranodal migration within a complex chemokine environment.
Main Methods:
- Combining tissue clearing with volumetric light sheet fluorescent microscopy of intact lymph nodes.
- Analyzing intranodal migration patterns and T cell differentiation niches.
- Proposing microfluidic chambers for studying chemokine environments.
Main Results:
- Short-lived effector cells (TSLEC) are imprinted in peripheral lymph node interfollicular regions, driven by CXCR3 migration.
- Stem-like memory cell (TSCM) differentiation is determined in the T cell paracortex.
- CCR7-directed segregation of precursors away from inflammatory niches promotes TSCM differentiation.
Conclusions:
- Intranodal migration spatially dictates CD8+ T cell differentiation into distinct effector and memory lineages.
- Chemokine signaling, particularly CCR7 and CXCR3, plays a critical role in spatial T cell fate determination.
- Future research combining microfluidics and advanced microscopy can elucidate the complex chemokine orchestration of T cell migration and differentiation.
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